Docetaxel is an anti-neoplastic agent of taxoid family and is well-known to exhibit anti-tumor and antileukaemic properties. Presently, it is sold under the trade name TAXOTERE®.
DOCETAXEL is the generic name for the compound (2R,3S)—N-carboxy-3-phenylisoserine, N-tert-butyl ester, 13-ester with 5(β)-20-epoxy-1,2(α),4,7(β),10(β),13(α)-hexahydroxy tax-11-en-9-one 4-acetate 2-benzoate, trihydrate and is represented by the formula (I)

Quite often, the key starting material used for preparing docetaxel is 10-DAB (10-De-acetyl Baccatin), which is extracted from the needles of the yew plant (Taxus baccata). Since in 10-DAB, which is possessing many hydroxy groups and all hydroxy groups are not equally reactive under the same reaction conditions, it is quite unpredictable as to which particular condition may work and industrially viable for the desired selective derivatization during the conversion of 10-DAB to taxane/taxane derivatives like docetaxel or paclitaxel.
In particular for docetaxel, vast literature reveals that the preparation of docetaxel from 10-DAB requires quite often selective protection of the C (7) and the C(10) hydroxy groups before the attachment of the side chain at C(13) hydroxy function.
Senilh et al. in C.R. Acad. Sci. Paris, IT, 1981, 293,501 observed that the relative reactivity of the four hydroxy groups in the 10-DAB is C (7)-OH>C (10)-OH>C(13)-OH>C(1)-OH towards acetic anhydride in pyridine, indicating that C (7)-OH reactivity magnitude is among the highest.
Holten et al. in U.S. Pat. No. 6,191,287 disclosed that the relative reactivity of C (7) and C (10) in 10 DAB is different for acetic anhydride in the presence of a lewis acid than a base. C (10) hydroxy group may be protected prior to the C (7) hydroxy group. Holten et al. described a process for acylating or silylating the C (10) hydroxy group prior to acylating, silylating or ketalizing the C (7) hydroxy group.
In European patent application EP 253,738B1 and its corresponding equivalent U.S. Pat. No. 4,814,470, the product of general formula (I) and their preparation have been described as first synthesis involving the use of cinnamoyl chloride for side chain incorporation based on the following synthetic scheme—

Colin et al in U.S. Pat. No. 4,924,012 disclose a process for preparing docetaxel, wherein an acid such as threo-2-(1-Ethoxyethoxy)-3-tert-butyloxycarbonylamino-3-phenylpropionic acid is condensed with a taxane derivative in which R2 is an acetyl group or a hydroxy-protecting group and R3 is a hydroxy-protecting group, and the protecting groups R1, R3 and where appropriate R2 is replaced by hydrogen.
The removal of the protecting groups from the ester obtained was accomplished by means of zinc in the presence of acetic acid at a temperature of between 30° and 60° C. or by treatment by means of an acid (inorganic or organic) such as hydrochloric acid or acetic acid dissolved in an aliphatic alcohol containing 1 to 3 carbon atoms in the presence of zinc. The reaction may be summarized based on the following synthetic scheme—

Fouque et al in U.S. Pat. No. 6,596,880 disclosed the method for the preparation of taxane derivatives including docetaxel comprising esterification at a temperature between −10 and 60° C. of a derivative of baccatin-III or 10-deacetyl baccatin-III of general formula (II) by means of an acid of general formula (III), followed by replacement of the protective groupings of the resulting product by hydrogen atoms.
The reaction may be summarized based on the following synthetic scheme—

The specification particularly describes the following specific aspects of the process of invention the as—                i. Esterification of the alcohol of general formula (II) using the acid of general formula (III)                    may be performed at a temperature preferably between 20 and 35° C.                        ii. For esterification, Esters and aromatic hydrocarbons are very particularly advantageous.        iii. In general formula (II) and (III), the protecting groups G1, G2 and R2 are selected from                    a. G1—2,2,2-trichloroethoxycarbonyl radical or a trialkylsilyl radical in which each                            alkyl part contains 1 to 4 carbon atoms,                                    b. G2—2,2,2-trichloroethoxycarbonyl radical            c. R2— methoxymethyl, 1-ethoxyethyl, benzyloxymethyl, (β-trimethyl silyl ethoxy)methyl,                            tetrahydropyranyl, 2,2,2-trichloroethoxymethyl or 2,2,2-trichloro                ethoxy carbonyl radical                                                iv. Replacement of the protecting groups by hydrogen atoms is carried out using zinc in acetic                    acid or by hydrolysis in an acidic medium.                        
Kanazawa et al in J. Org. Chem. 1994, 59, 1238-1240 disclosed another process for preparing docetaxel from the side chain free acid (A) with reasonably high efficiency based on the following synthetic scheme—

Its esterification with 7,10-bis[(2,2,2-trichloroethoxy)carbonyl]-10-desacetylbaccatin III was carried out in toluene with DCC and DMAP to provide after purification the triply protected docetaxel derivative. This triply protected docetaxel derivative is deprotected into Docetaxel through first treatment with zinc copper couple in acetic acid-methanol and then with hydrogen in the presence of palladium black.
However, in this process, docetaxel so produced was found to be contaminated with up to 15% of the corresponding 2'S (epimer) derivative. The formation of this epimer, which occurs during esterification, is apparently unavoidable and their removal required a tedious and industrially non viable chromatographic means. Though there have been many advances in the field especially utilizing direct coupling with open chain isoserine derivatives as well as indirect ways involving blocked side chains like oxazolidone, β-lactam, Oxazoline, Oxazinone and the like and later on opening the blocked side chain ring structures, however, there still remains a need for new or improved, economically viable processes for the preparation of docetaxel, which may be simple and amenable to scale up. The present invention addresses these needs and provides further related advantages like less epimer impurities formation and simple workup in the steps.